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https://www.readbyqxmd.com/read/28550802/mechanism-of-action-of-three-newly-registered-drugs-for-multiple-sclerosis-treatment
#1
REVIEW
Kaja Kasarełło, Agnieszka Cudnoch-Jędrzejewska, Andrzej Członkowski, Dagmara Mirowska-Guzel
Multiple sclerosis (MS) is a disease of suspected autoimmune origin leading to neurodegeneration. The disease pathomechanism is considered to be primarily based on neuroinflammation directed against myelin antigens caused by autoreactive T cells. MS etiology remains still unknown, which makes it difficult to create an efficient therapy, therefore, MS treatment targets mechanisms involved in disease pathology. In this review, we present the mechanism of action of three newly registered drugs for MS. Dimethyl fumarate (DMF) is an agent presenting a broad spectrum of action...
February 22, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28549068/oligodendroglial-myelination-requires-astrocyte-derived-lipids
#2
Nutabi Camargo, Andrea Goudriaan, Anne-Lieke F van Deijk, Willem M Otte, Jos F Brouwers, Hans Lodder, David H Gutmann, Klaus-Armin Nave, Rick M Dijkhuizen, Huibert D Mansvelder, Roman Chrast, August B Smit, Mark H G Verheijen
In the vertebrate nervous system, myelination of axons for rapid impulse propagation requires the synthesis of large amounts of lipids and proteins by oligodendrocytes and Schwann cells. Myelin membranes are thought to be cell-autonomously assembled by these axon-associated glial cells. Here, we report the surprising finding that in normal brain development, a substantial fraction of the lipids incorporated into central nervous system (CNS) myelin are contributed by astrocytes. The oligodendrocyte-specific inactivation of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP), an essential coactivator of the transcription factor SREBP and thus of lipid biosynthesis, resulted in significantly retarded CNS myelination; however, myelin appeared normal at 3 months of age...
May 2017: PLoS Biology
https://www.readbyqxmd.com/read/28548612/multiple-sclerosis-serum-anti-cns-autoantibodies
#3
John W Prineas, John D E Parratt
BACKGROUND: It is uncertain whether there are autoantibodies detectable by indirect immunofluorescence in the serum of patients with multiple sclerosis (MS). OBJECTIVE: To determine whether there are anti-central nervous system (CNS) autoantibodies detectable by indirect immunofluorescence in the serum of MS patients. METHODS: Sera and in some cases cerebrospinal fluid from 106 patients with multiple sclerosis, 156 patients with other neurological diseases, and 70 healthy control subjects were examined by indirect immunofluorescence using cryostat sections of rat cerebrum fixed by perfusion with paraformaldehyde...
May 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28548216/pathology-of-oligodendroglia-an-overview
#4
Takashi Komori
Oligodendroglia are cells responsible for creating myelin sheaths for axons in the CNS. However, pathologies of oligodendroglia other than demyelination are not well understood due to the lack of adequate methods of characterizing pathological conditions affecting oligodendroglia in human tissue. This review discusses three major topics with the aim of clarifying some of the controversies in the study of oligodendroglia. The oligodendroglioma, a relatively indolent form of diffuse gliomas thought to originate in oligodendrocytes, has never demonstrated myelin formation on electron microscopy nor shown a constant expression of myelin-related proteins...
May 26, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28547865/re-imagining-alzheimer-s-disease-the-diminishing-importance-of-amyloid-and-a-glimpse-of-what-lies-ahead
#5
REVIEW
Kai-Hei Tse, Karl Herrup
Many have criticized the amyloid cascade hypothesis of Alzheimer's disease for its inconsistencies and failures to either accurately predict disease symptoms or guide the development of productive therapies. In addition to criticisms, however, we believe that the field would benefit from having alternative narratives and disease models that can either replace or function alongside of an amyloid-centric view of Alzheimer's. This review is an attempt to meet that need. We offer three experimentally verified amyloid-independent mechanisms, each of which plausibly contributes substantially to the etiology of Alzheimer's disease: loss of DNA integrity, faulty cell cycle regulation, regression of myelination...
May 26, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28546087/region-specific-oligodendrocyte-transcription-factor-expression-in-a-model-of-neonatal-hypoxic-injury
#6
Bethann M Affeldt, Andre Obenaus, Jonathan Chan, Andrea C Pardo
White matter injury (WMI) of prematurity is associated with a spectrum of neurological disorders ranging from mild cognitive and behavioral deficits to cerebral palsy. Translational studies have implicated impaired oligodendrocyte development after hypoxia as the primary cause of WMI, but the underlying mechanisms remain poorly understood. The goal of this study was to identify alterations in the expression of oligodendrocyte precursor cell transcription factors in a mouse model of transient mild global hypoxia...
May 22, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28545922/diseases-of-connexins-expressed-in-myelinating-glia
#7
REVIEW
Charles K Abrams
Connexins are a family of integral membrane proteins most of which form gap junctions and many of which form hemichannels as well. Mutations in at least 9 of the 21 genes encoding human connexin proteins cause human diseases. Mutations in GJB1 (Cx32), expressed in both Schwann cells and oligodendrocytes, cause both a form of inherited peripheral neuropathy and a variety of CNS symptoms. Mutations in GJC2 (Cx47), expressed only in oligodendrocytes within the nervous system, cause a severe early onset dysmyelinating disorder, Pelizaeus-Merzbacher-Like disease (PMLD1 or HLD2), hereditary spastic paraplegia (SPG44), which has a milder phenotype and later onset, and a subclinical leukodystrophy...
May 22, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28545594/early-blockade-of-joint-inflammation-with-a-fatty-acid-amide-hydrolase-inhibitor-decreases-end-stage-osteoarthritis-pain-and-peripheral-neuropathy-in-mice
#8
Jason J McDougall, Milind M Muley, Holly T Philpott, Allison Reid, Eugene Krustev
BACKGROUND: The endocannabinoid system has been shown to reduce inflammatory flares and pain in rodent models of arthritis. A limitation of endocannabinoids is that they are rapidly denatured by hydrolysing enzymes such as fatty acid amide hydrolase (FAAH) which renders them physiologically inert. Osteoarthritis (OA) is primarily a degenerative joint disease; however, it can incorporate mild inflammation and peripheral neuropathy. The aim of this study was to determine whether early blockade of FAAH bioactivity could reduce OA-associated inflammation and joint neuropathy...
May 25, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28545015/motor-unit-number-index-munix-in-patients-with-anti-mag-neuropathy
#9
Farzad Fatehi, Emilien Delmont, Aude-Marie Grapperon, Emmanuelle Salort-Campana, Amandine Sévy, Annie Verschueren, José Boucraut, Shahram Attarian
OBJECTIVE: To investigate the relationship between Motor Unit Number Index (MUNIX) and functional scales in patients with anti-Myelin Associated Glycoprotein (MAG) neuropathy and to know if MUNIX is modify after rituximab (RTX) therapy. METHODS: 17 patients were enrolled, of whom 6 were prospectively evaluated during one year after RTX treatment. MUNIX technique was assessed in abductor digiti mini (ADM), abductor pollicis brevi (APB) and tibialis anterior (TA) muscles...
May 9, 2017: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/28544974/cetuximab-modified-collagen-scaffold-directs-neurogenesis-of-injury-activated-endogenous-neural-stem-cells-for-acute-spinal-cord-injury-repair
#10
Xing Li, Yannan Zhao, Shixiang Cheng, Sufang Han, Muya Shu, Bing Chen, Xuyi Chen, Fengwu Tang, Nuo Wang, Yue Tu, Bin Wang, Zhifeng Xiao, Sai Zhang, Jianwu Dai
Studies have shown that endogenous neural stem cells (NSCs) activated by spinal cord injury (SCI) primarily generate astrocytes to form glial scar. The NSCs do not differentiate into neurons because of the adverse microenvironment. In this study, we defined the activation timeline of endogenous NSCs in rats with severe SCI. These injury-activated NSCs then migrated into the lesion site. Cetuximab, an EGFR signaling antagonist, significantly increased neurogenesis in the lesion site. Meanwhile, implanting cetuximab modified linear ordered collagen scaffolds (LOCS) into SCI lesion sites in dogs resulted in neuronal regeneration, including neuronal differentiation, maturation, myelination, and synapse formation...
May 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28544286/early-regional-cuprizone-induced-demyelination-in-a-rat-model-revealed-with-mri
#11
Wendy Oakden, Nicholas A Bock, Alia Al-Ebraheem, Michael J Farquharson, Greg J Stanisz
The cuprizone model of demyelination is well established in the mouse as a tool for the study of the mechanisms of both demyelination and remyelination. It is often desirable, however, to have a larger model, such as the rat, especially for imaging-based studies, yet initial work has failed to show demyelination in cuprizone-fed rats. Several recent studies have demonstrated demyelination in the rat, but only in the corpus callosum. In this study, we acquired high-resolution, three-dimensional images of the whole brain every 2 weeks, using a T1 -weighted magnetization-prepared rapid acquisition gradient echo imaging sequence, optimized for myelin contrast, in order to assess myelination across the entire rat brain over a period of 8 weeks on a 1% cuprizone diet...
May 22, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28543723/neuromuscular-junctions-nmjs-ultrastructural-analysis-and-nicotinic-acetylcholine-receptor-nachr-subunit-mrna-expression-in-offspring-subjected-to-protein-restriction-throughout-pregnancy
#12
Paula Aiello Tomé de Souza Castro, Ludimila Canuto Faccioni, Patrícia Aline Boer, Robson Francisco Carvalho, Selma Maria Michelin Matheus, Maeli Dal-Pai-Silva
Protein restriction during gestation can alter the skeletal muscle phenotype of offspring; however, little is known with regard to whether this also affects the neuromuscular junction (NMJ), as muscle phenotype maintenance depends upon NMJ functional integrity. This study aimed to evaluate the effects of a low protein (6%) intake by dams throughout gestation on male offspring NMJ morphology and nicotinic acetylcholine receptor (nAChR) α1, γ and ε subunit expression in the soleus (SOL) and extensor digitorum longus (EDL) muscles...
May 25, 2017: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/28543541/human-schwann-cells-exhibit-long-term-cell-survival-are-not-tumorigenic-and-promote-repair-when-transplanted-into-the-contused-spinal-cord
#13
Johana Bastidas, Gagani Athauda, Gabriela De La Cruz, Wai-Man Chan, Roozbeh Golshani, Yerko Berrocal, Martha Henao, Anil Lalwani, Chikato Mannoji, Mazen Assi, P Anthony Otero, Aisha Khan, Alexander E Marcillo, Michael Norenberg, Allan D Levi, Patrick M Wood, James D Guest, W Dalton Dietrich, Mary Bartlett Bunge, Damien D Pearse
The transplantation of rodent Schwann cells (SCs) provides anatomical and functional restitution in a variety of spinal cord injury (SCI) models, supporting the recent translation of SCs to phase 1 clinical trials for human SCI. Whereas human (Hu)SCs have been examined experimentally in a complete SCI transection paradigm, to date the reported behavior of SCs when transplanted after a clinically relevant contusive SCI has been restricted to the use of rodent SCs. Here, in a xenotransplant, contusive SCI paradigm, the survival, biodistribution, proliferation and tumorgenicity as well as host responses to HuSCs, cultured according to a protocol analogous to that developed for clinical application, were investigated...
May 22, 2017: Glia
https://www.readbyqxmd.com/read/28542521/regeneration-of-myelin-sheaths-of-normal-length-and-thickness-in-the-zebrafish-cns-correlates-with-growth-of-axons-in-caliber
#14
Marja J Karttunen, Tim Czopka, Marieke Goedhart, Jason J Early, David A Lyons
Demyelination is observed in numerous diseases of the central nervous system, including multiple sclerosis (MS). However, the endogenous regenerative process of remyelination can replace myelin lost in disease, and in various animal models. Unfortunately, the process of remyelination often fails, particularly with ageing. Even when remyelination occurs, it is characterised by the regeneration of myelin sheaths that are abnormally thin and short. This imperfect remyelination is likely to have implications for the restoration of normal circuit function and possibly the optimal metabolic support of axons...
2017: PloS One
https://www.readbyqxmd.com/read/28542067/grb2-associated-binder-1-is-required-for-extrafusal-and-intrafusal-muscle-fiber-development
#15
So Y Park, So Y Jang, Yoon K Shin, Byeol A Yoon, Hye J Lee, Hwan T Park
The neuregulin-1 (NRG1) signaling pathway plays an important role in the development of the peripheral neuromuscular system, including in muscle spindle and postnatal myelination. We previously showed that NRG1 on the axonal membrane regulates peripheral nerve myelination through Grb2-associated binder 1 (Gab1), a scaffolding mediator of receptor tyrosine kinase signaling. Here, we determined the role of Gab1 in the development of muscles and the muscle spindle using muscle-specific conditional Gab1 knockout mice...
May 24, 2017: Neuroreport
https://www.readbyqxmd.com/read/28541151/morphological-evaluation-of-merkel-cells-and-small-lamellated-sensory-receptors-in-the-equine-foot
#16
Robert M Bowker, Lisa S Lancaster, Diane A Isbell
OBJECTIVE To examine the equine foot for the presence of sensory receptors including Merkel cells and small lamellated Pacinian-like corpuscles (SLPCs). SAMPLE Forefeet obtained from 7 horses following euthanasia for reasons other than foot disease. PROCEDURES Disarticulated feet were cut into either sagittal sections or cross sections and immersed in neutral-buffered 4% formalin. Following fixation, samples were obtained from the midline of the dorsal aspect of the hoof wall and from the frog (cuneus ungulae) between the apex and central sulcus...
June 2017: American Journal of Veterinary Research
https://www.readbyqxmd.com/read/28536996/models-for-studying-myelination-demyelination-and-remyelination
#17
REVIEW
I Osorio-Querejeta, M Sáenz-Cuesta, M Muñoz-Culla, D Otaegui
One of the most widely studied demyelinating diseases is multiple sclerosis, which is characterised by the appearance of demyelinating plaques, followed by myelin regeneration. Nevertheless, with disease progression, remyelination tends to fail, increasing the characteristic neurodegeneration of the disease. It is essential to understand the mechanisms that operate in the processes of myelination, demyelination and remyelination to develop treatments that promote the production of new myelin, thereby protecting the central nervous system...
May 23, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28536506/axonal-membranes-and-their-domains-assembly-and-function-of-the-axon-initial-segment-and-node-of-ranvier
#18
REVIEW
Andrew D Nelson, Paul M Jenkins
Neurons are highly specialized cells of the nervous system that receive, process and transmit electrical signals critical for normal brain function. Here, we review the intricate organization of axonal membrane domains that facilitate rapid action potential conduction underlying communication between complex neuronal circuits. Two critical excitable domains of vertebrate axons are the axon initial segment (AIS) and the nodes of Ranvier, which are characterized by the high concentrations of voltage-gated ion channels, cell adhesion molecules and specialized cytoskeletal networks...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28535786/biochemical-markers-in-vascular-cognitive-impairment-associated-with-subcortical-small-vessel-disease-a-consensus-report
#19
A Wallin, E Kapaki, M Boban, S Engelborghs, D M Hermann, B Huisa, M Jonsson, M G Kramberger, L Lossi, B Malojcic, S Mehrabian, A Merighi, E B Mukaetova-Ladinska, G P Paraskevas, B O Popescu, R Ravid, L Traykov, G Tsivgoulis, G Weinstein, A Korczyn, M Bjerke, G Rosenberg
BACKGROUND: Vascular cognitive impairment (VCI) is a heterogeneous entity with multiple aetiologies, all linked to underlying vascular disease. Among these, VCI related to subcortical small vessel disease (SSVD) is emerging as a major homogeneous subtype. Its progressive course raises the need for biomarker identification and/or development for adequate therapeutic interventions to be tested. In order to shed light in the current status on biochemical markers for VCI-SSVD, experts in field reviewed the recent evidence and literature data...
May 23, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28535586/an-experimental-infarct-targeting-the-internal-capsule-histopathological-and-ultrastructural-changes
#20
Chang-Woo Han, Kyung-Hwa Lee, Myung Giun Noh, Jin-Myung Kim, Hyung-Seok Kim, Hyung-Sun Kim, Ra Gyung Kim, Jongwook Cho, Hyoung-Ihl Kim, Min-Cheol Lee
BACKGROUND: Stroke involving the cerebral white matter (WM) has increased in prevalence, but most experimental studies have focused on ischemic injury of the gray matter. This study was performed to investigate the WM in a unique rat model of photothrombotic infarct targeting the posterior limb of internal capsule (PLIC), focusing on the identification of the most vulnerable structure in WM by ischemic injury, subsequent glial reaction to the injury, and the fundamental histopathologic feature causing different neurologic outcomes...
May 2017: Journal of Pathology and Translational Medicine
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